Translational Medical Research Commons^™

Social Determinants May Limit The Success Of Pcsk9 Inhibitors, An Effective Treatment For Hyperlipidemia In Statin-Intolerant Patients, Abigail C. Kuplicki

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Moriarty PM, Thompson PD, Cannon CP, et al. Efficacy and safety of alirocumab vs ezetimibe in statin-intolerant patients, with a statin rechallenge arm: The ODYSSEY ALTERNATIVE randomized trial. J. Clin. Lipidol. 2015;9(6):758-769. https://doi.org/10.1016/j.jacl.2015.08.006

for a statin-intolerant patient with hyperlipidemia.

Potential Benefits Of Combined Statin And Metformin Therapy On Resistance Training Response In Older Individuals, Douglas E. Long, Kate Kosmac, Cory M. Dungan, Marcas M. Bamman, Charlotte A. Peterson, Phillip A. Kern

Clinical and Translational Science Faculty Publications

Metformin and statins are currently the focus of large clinical trials testing their ability to counter age-associated declines in health, but recent reports suggest that both may negatively affect skeletal muscle response to exercise. However, it has also been suggested that metformin may act as a possible protectant of statin-related muscle symptoms. The potential impact of combined drug use on the hypertrophic response to resistance exercise in healthy older adults has not been described. We present secondary statin analyses of data from the MASTERS trial where metformin blunted the hypertrophy response in healthy participants (>65 years) following 14 weeks …

Simvastatin Induces Unfolded Protein Response And Enhances Temozolomide-Induced Cell Death In Glioblastoma Cells., Sanaz Dastghaib, Shahla Shojaei, Zohreh Mostafavi-Pour, Pawan Sharma, John B Patterson, Afshin Samali, Pooneh Mokarram, Saeid Ghavami

Center for Translational Medicine Faculty Papers

Glioblastoma (GBM) is the most prevalent malignant primary brain tumor with a very poor survival rate. Temozolomide (TMZ) is the common chemotherapeutic agent used for GBM treatment. We recently demonstrated that simvastatin (Simva) increases TMZ-induced apoptosis via the inhibition of autophagic flux in GBM cells. Considering the role of the unfolded protein response (UPR) pathway in the regulation of autophagy, we investigated the involvement of UPR in Simva-TMZ-induced cell death by utilizing highly selective IRE1 RNase activity inhibitor MKC8866, PERK inhibitor GSK-2606414 (PERKi), and eIF2α inhibitor salubrinal. Simva-TMZ treatment decreased the viability of GBM cells and significantly increased apoptotic cell …

Mechanisms Of Simvastatin Myotoxicity: The Role Of Autophagy Flux Inhibition., Arya Emami, Shahla Shojaei, Simone C. Da Silva Rosa, Mahmoud Aghaei, Ehsan Samiei, Amir Reza Vosoughi, Forouh Kalantari, Philip Kawalec, James Thliveris, Pawan Sharma, Amir A. Zeki, Mohsen Akbari, Joseph W. Gordon, Saeid Ghavami

Center for Translational Medicine Faculty Papers

Statins are some of the most widely used drugs worldwide, but one of their major side effects is myotoxicity. Using mouse myoblast (C2C12) and human alveolar rhabdomyosarcoma cell lines (RH30) in both 2-dimensional (2D) and 3-dimensional (3D) cell culture, we investigated the mechanisms of simvastatin's myotoxicity. We found that simvastatin significantly reduced cell viability in C2C12 cells compared to RH30 cells. However, simvastatin induced greater apoptosis in RH30 compared to C2C12 cells. Simvastatin-induced cell death is dependent on geranylgeranyl pyrophosphate (GGPP) in C2C12 cells, while in RH30 cells it is dependent on both farnesyl pyrophosphate (FPP) and GGPP. Simvastatin inhibited …

Statin Therapy For Elderly Patients Should Be Assessed For Each Individual, Raymond Gong

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Shepherd J, Blauw GJ, Murphy MB, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002;360(9346):1623-30. doi:10.1016/S0140-6736(02)11600-X